One of the distinguishing features of alpha herpesviruses is their propensity to infect and then establish latency in sensory ganglion cells. The initial portion of this project aims at determining whether there are specific subpopulations of dorsal root ganglion (DRG) neurons, as characterized by their morphology, connections and neuropeptide content, that initially become infected following herpes simplex virus type-2 (HSV-2) inoculation and later harbor latent virus. Major findings are: 1) Route of inoculation plays an important role in determining which populations of DRG neurons are acutely Infected. Peripheral inoculation establishes HSV-2 infection in the small subpopulation, while intraneural injection targets a slightly broader spectrum of cell sizes. 2) Modification of host cell peptide production is not detectable with immunocytochemical methods during the acute phase of infection. In situ hybridization histochemistry for peptide mRNA would be a more sensitive indicator and will be examined. 3) HSV-2 strains differing in virulence affect the numbers of DRG cells that express viral antigen, but not the specific subpopulation. The effects of HSV-2 inoculation route and virus strain on the latent phase of DRG infection will next be examined. These experiments lay the groundwork for the interpretation of subsequent central and peripheral nervous system regeneration studies in a herpesvirus model.